Association analysis of schizophrenia on 18 genes involved in neuronal migration: MDGA1 as a new susceptibility gene

Anna K Kähler; Srdjan Djurovic; Bettina Kulle; Erik G Jönsson; Ingrid Agartz; Håkan Hall; Stein Opjordsmoen; Klaus D Jakobsen; Thomas Hansen; Ingrid Melle; Thomas Werge; Vidar M Steen; Ole A Andreassen

doi:http://dx.doi.org/10.1002/ajmg.b.30726

Association analysis of schizophrenia on 18 genes involved in neuronal migration: MDGA1 as a new susceptibility gene

Anna K Kähler, Srdjan Djurovic, Bettina Kulle, Erik G Jönsson, Ingrid Agartz, Håkan Hall, Stein Opjordsmoen, Klaus D Jakobsen, Thomas Hansen, Ingrid Melle, Thomas Werge, Vidar M Steen, Ole A Andreassen

89 Citationer (Scopus)

Abstract

Several lines of evidence support the theory of schizophrenia (SZ) being a neurodevelopmental disorder. The structural, cytoarchitectural and functional brain abnormalities reported in patients with SZ, might be due to aberrant neuronal migration, since the final position of neurons affects neuronal function, morphology, and formation of synaptic connections. We have investigated the putative association between SZ and gene variants engaged in the neuronal migration process, by performing an association study on 839 cases and 1,473 controls of Scandinavian origin. Using a gene-wide approach, tagSNPs in 18 candidate genes have been genotyped, with gene products involved in the neuron-to-glial cell adhesion, interactions with the DISC1 protein and/or rearrangements of the cytoskeleton. Of the 289 markers tested, 19 markers located in genes MDGA1, RELN, ITGA3, DLX1, SPARCL1, and ASTN1, attained nominal significant P-values (P <0.05) in either a genotypic or allelic association test. All of these genes, except transcription factor DLX1, are involved in the adhesion between neurons and radial glial cells. Eight markers obtained nominal significance in both tests, and were located in intronic or 3'UTR regions of adhesion molecule MDGA1 and previously reported SZ candidate RELN. The most significant result was attained for MDGA1 SNP rs9462341 (unadjusted association results: genotypic P = 0.00095; allelic P = 0.010). Several haplotypes within MDGA1, RELN, ITGA3, and ENAH were nominally significant. Further studies in independent samples are needed, including upcoming genome wide association study results, but our data suggest that MDGA1 is a new SZ susceptibility gene, and that altered neuronal migration is involved in SZ pathology.

Originalsprog	Engelsk
Tidsskrift	American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics
Vol/bind	147B
Udgave nummer	7
Sider (fra-til)	1089-100
Antal sider	12
ISSN	1552-4841
DOI	https://doi.org/10.1002/ajmg.b.30726
Status	Udgivet - 2008

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http://dx.doi.org/10.1002/ajmg.b.30726

Citationsformater

Kähler, A. K., Djurovic, S., Kulle, B., Jönsson, E. G., Agartz, I., Hall, H., Opjordsmoen, S., Jakobsen, K. D., Hansen, T., Melle, I., Werge, T., Steen, V. M., & Andreassen, O. A. (2008). Association analysis of schizophrenia on 18 genes involved in neuronal migration: MDGA1 as a new susceptibility gene. American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics, 147B(7), 1089-100. https://doi.org/10.1002/ajmg.b.30726

Association analysis of schizophrenia on 18 genes involved in neuronal migration : MDGA1 as a new susceptibility gene. / Kähler, Anna K; Djurovic, Srdjan; Kulle, Bettina et al.

I: American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics, Bind 147B, Nr. 7, 2008, s. 1089-100.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

Kähler, AK, Djurovic, S, Kulle, B, Jönsson, EG, Agartz, I, Hall, H, Opjordsmoen, S, Jakobsen, KD, Hansen, T, Melle, I, Werge, T, Steen, VM & Andreassen, OA 2008, 'Association analysis of schizophrenia on 18 genes involved in neuronal migration: MDGA1 as a new susceptibility gene', American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics, bind 147B, nr. 7, s. 1089-100. https://doi.org/10.1002/ajmg.b.30726

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title = "Association analysis of schizophrenia on 18 genes involved in neuronal migration: MDGA1 as a new susceptibility gene",

abstract = "Several lines of evidence support the theory of schizophrenia (SZ) being a neurodevelopmental disorder. The structural, cytoarchitectural and functional brain abnormalities reported in patients with SZ, might be due to aberrant neuronal migration, since the final position of neurons affects neuronal function, morphology, and formation of synaptic connections. We have investigated the putative association between SZ and gene variants engaged in the neuronal migration process, by performing an association study on 839 cases and 1,473 controls of Scandinavian origin. Using a gene-wide approach, tagSNPs in 18 candidate genes have been genotyped, with gene products involved in the neuron-to-glial cell adhesion, interactions with the DISC1 protein and/or rearrangements of the cytoskeleton. Of the 289 markers tested, 19 markers located in genes MDGA1, RELN, ITGA3, DLX1, SPARCL1, and ASTN1, attained nominal significant P-values (P <0.05) in either a genotypic or allelic association test. All of these genes, except transcription factor DLX1, are involved in the adhesion between neurons and radial glial cells. Eight markers obtained nominal significance in both tests, and were located in intronic or 3'UTR regions of adhesion molecule MDGA1 and previously reported SZ candidate RELN. The most significant result was attained for MDGA1 SNP rs9462341 (unadjusted association results: genotypic P = 0.00095; allelic P = 0.010). Several haplotypes within MDGA1, RELN, ITGA3, and ENAH were nominally significant. Further studies in independent samples are needed, including upcoming genome wide association study results, but our data suggest that MDGA1 is a new SZ susceptibility gene, and that altered neuronal migration is involved in SZ pathology.",

author = "K{\"a}hler, {Anna K} and Srdjan Djurovic and Bettina Kulle and J{\"o}nsson, {Erik G} and Ingrid Agartz and H{\aa}kan Hall and Stein Opjordsmoen and Jakobsen, {Klaus D} and Thomas Hansen and Ingrid Melle and Thomas Werge and Steen, {Vidar M} and Andreassen, {Ole A}",

year = "2008",

doi = "http://dx.doi.org/10.1002/ajmg.b.30726",

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pages = "1089--100",

journal = "American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics",

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TY - JOUR

T1 - Association analysis of schizophrenia on 18 genes involved in neuronal migration

T2 - MDGA1 as a new susceptibility gene

AU - Kähler, Anna K

AU - Djurovic, Srdjan

AU - Kulle, Bettina

AU - Jönsson, Erik G

AU - Agartz, Ingrid

AU - Hall, Håkan

AU - Opjordsmoen, Stein

AU - Jakobsen, Klaus D

AU - Hansen, Thomas

AU - Melle, Ingrid

AU - Werge, Thomas

AU - Steen, Vidar M

AU - Andreassen, Ole A

PY - 2008

Y1 - 2008

N2 - Several lines of evidence support the theory of schizophrenia (SZ) being a neurodevelopmental disorder. The structural, cytoarchitectural and functional brain abnormalities reported in patients with SZ, might be due to aberrant neuronal migration, since the final position of neurons affects neuronal function, morphology, and formation of synaptic connections. We have investigated the putative association between SZ and gene variants engaged in the neuronal migration process, by performing an association study on 839 cases and 1,473 controls of Scandinavian origin. Using a gene-wide approach, tagSNPs in 18 candidate genes have been genotyped, with gene products involved in the neuron-to-glial cell adhesion, interactions with the DISC1 protein and/or rearrangements of the cytoskeleton. Of the 289 markers tested, 19 markers located in genes MDGA1, RELN, ITGA3, DLX1, SPARCL1, and ASTN1, attained nominal significant P-values (P <0.05) in either a genotypic or allelic association test. All of these genes, except transcription factor DLX1, are involved in the adhesion between neurons and radial glial cells. Eight markers obtained nominal significance in both tests, and were located in intronic or 3'UTR regions of adhesion molecule MDGA1 and previously reported SZ candidate RELN. The most significant result was attained for MDGA1 SNP rs9462341 (unadjusted association results: genotypic P = 0.00095; allelic P = 0.010). Several haplotypes within MDGA1, RELN, ITGA3, and ENAH were nominally significant. Further studies in independent samples are needed, including upcoming genome wide association study results, but our data suggest that MDGA1 is a new SZ susceptibility gene, and that altered neuronal migration is involved in SZ pathology.

AB - Several lines of evidence support the theory of schizophrenia (SZ) being a neurodevelopmental disorder. The structural, cytoarchitectural and functional brain abnormalities reported in patients with SZ, might be due to aberrant neuronal migration, since the final position of neurons affects neuronal function, morphology, and formation of synaptic connections. We have investigated the putative association between SZ and gene variants engaged in the neuronal migration process, by performing an association study on 839 cases and 1,473 controls of Scandinavian origin. Using a gene-wide approach, tagSNPs in 18 candidate genes have been genotyped, with gene products involved in the neuron-to-glial cell adhesion, interactions with the DISC1 protein and/or rearrangements of the cytoskeleton. Of the 289 markers tested, 19 markers located in genes MDGA1, RELN, ITGA3, DLX1, SPARCL1, and ASTN1, attained nominal significant P-values (P <0.05) in either a genotypic or allelic association test. All of these genes, except transcription factor DLX1, are involved in the adhesion between neurons and radial glial cells. Eight markers obtained nominal significance in both tests, and were located in intronic or 3'UTR regions of adhesion molecule MDGA1 and previously reported SZ candidate RELN. The most significant result was attained for MDGA1 SNP rs9462341 (unadjusted association results: genotypic P = 0.00095; allelic P = 0.010). Several haplotypes within MDGA1, RELN, ITGA3, and ENAH were nominally significant. Further studies in independent samples are needed, including upcoming genome wide association study results, but our data suggest that MDGA1 is a new SZ susceptibility gene, and that altered neuronal migration is involved in SZ pathology.

U2 - http://dx.doi.org/10.1002/ajmg.b.30726

DO - http://dx.doi.org/10.1002/ajmg.b.30726

M3 - Journal article

SN - 1552-4841

VL - 147B

SP - 1089

EP - 1100

JO - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics

JF - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics

IS - 7

ER -

Association analysis of schizophrenia on 18 genes involved in neuronal migration: MDGA1 as a new susceptibility gene

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